Side Effects of Atrovent HFA (ipratropium bromide)

Atrovent HFA (ipratropium bromide) is a bronchodilator that dilates (enlarges) airways (bronchi) in the lungs. It is used in treating symptoms of asthma, colds, allergies, and chronic obstructive pulmonary disease (COPD) due to emphysema or chronic bronchitis. 

Atrovent HFA blocks the effect of acetylcholine on airways (bronchi) and nasal passages. Acetylcholine is a chemical that nerves use to communicate with muscle cells. 

In asthma and chronic obstructive pulmonary disease, cholinergic nerves going to the lungs cause narrowing of the airways by stimulating muscles surrounding the airways to contract. The "anti-cholinergic" effect of Atrovent HFA blocks the effect of cholinergic nerves, causing the muscles to relax and airways to dilate. 

Mucus glands in the nose also are controlled by nerves that use acetylcholine to communicate. By blocking acetylcholine, Atrovent HFA helps relieve symptoms of allergies and the common cold by preventing secretion of mucus by mucus glands in the nose. When inhaled, Atrovent HFA travels directly to airways, and very little is absorbed into the body. 

Common side effects of Atrovent HFA include

• dry mouth,
• cough,
• headache,
• nausea,
• dizziness, and
• difficulty breathing. 

Serious side effects of Atrovent HFA include

• bronchospasms that can be life-threatening,
• rash,
• itching, or
• serious allergic reactions involving closure of the airways, and may worsen symptoms of benign prostatic hyperplasia and narrow-angle glaucoma.

Drug interactions of Atrovent HFA include other anticholinergic drugs (for example, atropine) because it may increase the occurrence of side effects. 

There have been no studies of Atrovent HFA in humans during pregnancy. 

It is unknown if Atrovent HFA is secreted in breast milk. Other medications in the same class of drugs are secreted into breast milk. It is unknown if the small amounts that may appear in the milk are of any consequence to the infant. Consult your doctor before breastfeeding. 

The most common side effects associated with ipratropium are:

• dry mouth,
• cough,
• headache,
• nausea,
• dizziness, and
• difficulty breathing.

Ipratropium can cause bronchospasms that can be life-threatening. It can also cause rash, itching, or serious allergic reactions involving closure of the airways.

Because of its anticholinergic effect it may worsen symptoms of benign prostatic hyperplasia and narrow-angle glaucoma.

The following adverse reactions are described, or described in greater detail, in other sections:

• Hypersensitivity reactions, including anaphylaxis
• Paradoxical bronchospasm
• Ocular effects
• Urinary retention

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in patients.

Clinical Trials Experience

The adverse reaction information concerning Atrovent HFA is derived from two 12-week, double-blind, parallel group studies and one 1-year open-label, parallel group study. These studies compared Atrovent HFA Inhalation Aerosol, Atrovent CFC Inhalation Aerosol, and placebo (in one study only) in 1010 COPD patients.

The following table lists the incidence of adverse reactions that occurred at a rate of greater than or equal to 3% in any ipratropium bromide group and greater than placebo in the 12-week study. The frequency of corresponding reactions in the 1-year open label study is included for comparison.

TABLE 1 : Adverse Reactions (% Patients) in Atrovent HFA Clinical Trials

• Cough, rhinitis, and upper respiratory infection occurred in greater than or equal to 3% of patients in either ipratropium treatment group but not greater than placebo in the 12-week study.
• In the one open label controlled study in 456 COPD patients, the overall incidence of adverse events was also similar between Atrovent HFA and Atrovent CFC formulations.
• Overall, in the above mentioned studies, 9.3% of the patients taking 42 mcg Atrovent HFA and 8.7% of the patients taking 42 mcg Atrovent CFC reported at least one adverse event that was considered by the investigator to be related to the study drug. The most common drug-related adverse events were dry mouth (1.6% of Atrovent HFA and 0.9% of Atrovent CFC patients), and taste perversion (bitter taste) (0.9% of Atrovent HFA and 0.3% of Atrovent CFC patients).
• As an anticholinergic drug, cases of precipitation or worsening of narrow-angle glaucoma, glaucoma, halo vision, conjunctival hyperaemia, corneal edema, mydriasis, acute eye pain, dry throat, hypotension, palpitations, urinary retention, tachycardia, constipation, bronchospasm, including paradoxical bronchospasm have been reported with the use of Atrovent.
• Additional adverse reactions identified for Atrovent seen in clinical trials include throat irritation, stomatitis, mouth edema, and vision blurred.
• Allergic-type reactions such as skin rash, pruritus, angioedema including that of tongue, lips and face, urticaria (including giant urticaria), laryngospasm and anaphylactic reactions have been reported.

Post-Marketing Experience

• In a 5-year placebo-controlled trial, hospitalizations for supraventricular tachycardia and/or atrial fibrillation occurred with an incidence rate of 0.5% in COPD patients receiving Atrovent CFC.
• In addition to the adverse reactions reported in the controlled clinical trials, adverse reactions have been identified during post approval use of Atrovent.
• Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
• Allergic-type reactions such as skin rash, angioedema including that of tongue, lips and face, urticaria (including giant urticaria), laryngospasm and anaphylactic reactions have been reported, with positive rechallenge in some cases.
• Additionally, urinary retention, mydriasis, gastrointestinal distress (diarrhea, nausea, vomiting), cough and bronchospasm, including paradoxical bronchospasm, hypersensitivity reactions, intraocular pressure increased, accommodation disorder, heart rate increased, pharyngeal edema, and gastrointestinal motility disorders have been reported during the post-marketing period with use of Atrovent.

• Atrovent HFA has been used concomitantly with other drugs, including sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids commonly used in the treatment of chronic obstructive pulmonary disease.
• With the exception of albuterol, there are no formal studies fully evaluating the interaction effects of Atrovent HFA and these drugs with respect to safety and effectiveness.

Anticholinergic Agents

• There is potential for an additive interaction with concomitantly used anticholinergic medications.
• Therefore, avoid coadministration of Atrovent HFA with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects.